Glymphatic system clears extracellular tau and protects from tau aggregation and neurodegeneration

Accumulation of tau has been implicated in various neurodegenerative diseases termed tauopathies. Tau is a microtubule-associated protein but is also actively released into the extracellular fluids including brain interstitial fluid and cerebrospinal fluid (CSF). However, it remains elusive whether clearance of extracellular tau impacts tau-associated neurodegeneration. Here, we show that aquaporin-4 (AQP4), a major driver of the glymphatic clearance system, facilitates the elimination of extracellular tau from the brain to CSF and subsequently to deep cervical lymph nodes. Strikingly, deletion of AQP4 not only elevated tau in CSF but also markedly exacerbated phosphorylated tau deposition and the associated…

• JA
  Japan Agency for Medical Research and Development

  Award: JP20dm0207073
• NU
  Niigata University

  Award: 2021-20012
• N
  Nipro
• CR
  Core Research for Evolutional Science and Technology

  Award: JPMJCR18H3